Self-Attention Fully Convolutional DenseNets for Automatic Salt Segmentation.

3-D salt segmentation is important for many research topics spanning from exploration geophysics to structural geology. In seismic exploration, 3-D salt segmentation is directly related to the velocity modeling building that affects many processing steps, such as seismic migration and full waveform inversion. Manually picking the salt boundary becomes prohibitively time-consuming when the data size is too large. Here, we develop a highly generalized fully convolutional DenseNet for automatic salt segmentation. A squeeze-and-excitation network is used as a self-attention mechanism for guiding the proposed network to extract the most significant information related to the salt signals and discard the others. The proposed framework is a supervised technique and shows robust performance when applied to a new dataset using transfer learning and a small amount of training data. We test the robustness of the proposed framework on the Kaggle TGS salt segmentation dataset. To demonstrate the generalization ability of the framework, we further apply the trained model to an independent dataset synthesized from the 3-D SEAM model. We apply transfer learning to finely tune the trained model from the TGS dataset using only a small percentage of data from the 3-D SEAM dataset and obtain satisfactory results.

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers.

This study aims to use bioinformatics methods to determine the epigenetic changes in microRNA expression and DNA methylation caused by cigarette smoking. The data of mRNA, miRNA expression, and methylation microarray were obtained from the GEO database to filter differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and methylated CpG probes (DMPs) through the limma package. The R clusterProfile package was used for functional annotation and enrichment analysis. The protein-protein interaction (PPI) network was constructed by the String database and visualized in Cytoscape software. Starbase database was employed to predict lncRNA and CirRNA based on the sequence of miRNA, and to establish a regulatory network of ceRNA. By overlapping DEG and DEM, 107 down-miRNA-targeted up-regulated genes and 65 up-miRNA-target down-regulated genes were obtained, which were mainly enriched in autophagy signaling pathways and protein ubiquitination pathways, respectively. In addition, 324 genes with low methylation and high expression and 204 genes with high methylation and low expression were respectively related to the degeneration of the nervous system and the function of the cardiovascular system. Interestingly, 43 genes were up-regulated under the dual regulation of reduced miRNA and hypomethylation, while 14 genes were down-regulated under the dual regulation of increased miRNA and hypermethylation. Ten chemicals have been identified as putative therapeutic agents for pathological conditions caused by smoking. In addition, among these genes, HSPA4, GRB2, PRKCA, and BCL2L1 could play a fundamental role in related diseases caused by smoking and may be used as the biomarkers for precise diagnosis and targets for future therapies of smoking-related diseases.

Characterization of DNA methylation as well as mico-RNA expression and screening of epigenetic markers in adipogenesis.

This study aimed to use bioinformatics methods to characterize epigenetic changes in terms of micro-RNA(miRNA) expression and DNA methylation during adipogenesis. The mRNA and miRNA expression microarray and DNA methylation dataset were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated probes (DMPs) were filtered using the limma package. The R language cluster profile package was used for functional and enrichment analysis. A protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. The Connection map (CMap) website tool was used to screen potential therapeutic drugs for adipogenesis. When comparing the early and late stages of adipogenesis, 111 low miRNA targeted upregulated genes and 64 high miRNA targeted downregulated genes were obtained, as well as 663 low-methylated high-expressed genes and 237 high-methylated low-expressed genes. In addition, 41 genes (24 upregulated and 17 downregulated) were simultaneously regulated by abnormal miRNA changes and DNA methylation. Ten chemicals were identified as putative therapeutics for adipogenesis. In addition, among the dual-regulated genes identified, CANX, HNRNPA1, MCL1, and PPIF may play key roles in the epigenetic regulation of adipogenesis and may serve as aberrant methylation or miRNA targeting biomarkers.

Injectable Mussel-Inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration.

In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway. Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance.

Case series and finite element analysis of PFNA combined with cerclage wire for treatment of subtrochanteric fracture of femur.

OBJECTIVE: To retrospectively analyze the clinical efficacy of PFNA combined with a cerclage wire in the treatment of 52 patients with unstable subtrochanteric fracture of the femur and to analyze the biomechanical effect of ligature on a fracture model. METHODS: In this study, 52 patients with unstable subtrochanteric fractures were treated in our orthopedic trauma center from June 2013 to July 2018. The Seinsheimer type IV fracture model was established using the patient's CT data, and the joint surface of the distal femoral condyle and the external condyle were restrained. The femoral head was used as the loading point, and a force of 500 N was applied vertically along the long axis of the femoral shaft. RESULTS: All 52 patients were followed up for 12 to 37 months, with an average of 18.07 ± 4.38 months. According to the Sanders hip function score, 28 cases were excellent (55-60 points), 22 cases were good (45-54 points), and 2 cases were poor (35-44 points), with an excellent and good rate of 96.15%. Postoperative deep vein thrombosis occurred in 3 cases, and fracture nonunion occurred in 1 case. No infection, loose fracture of internal fixation or hip varus deformity occurred. The finite element analysis indicated that the displacement of the whole model decreased slightly and the relative sliding of the fracture block decreased, but the maximum stress of the femur increased after the addition of the cerclage wire. CONCLUSION: The treatment of unstable subtrochanteric fracture of the femur with PFNA combined with cerclage wire has the advantages of simple operation, satisfactory reduction of fracture, stable fixation, and good recovery of limb function. The finite element analysis suggested that the biomechanical strength fixation was enhanced after the addition of cerclage wire. However, the local stress concentration of the tie may increase the risk of failure.

Schisandrin A restrains osteoclastogenesis by inhibiting reactive oxygen species and activating Nrf2 signalling.

OBJECTIVES: Intracellular reactive oxygen species (ROS) induced by receptor activator of NF-kB ligand (RANKL) has been proven to be a critical factor in the development of osteoclasts. This study aimed to prove that schisandrin A (Sch), a novel anti-oxidant compound, is able to suppress osteoclastogenesis and prevent bone loss in ovariectomized (OVX) mice by suppressing ROS via nuclear factor erythroid 2-related factor (Nrf2). MATERIAL AND METHODS: Micro-CT was used to detect bone formation. The effects of Sch on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced reactive oxygen species (ROS) were measured by dihydroethidium (DHE) staining in vivo and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining in vitro. Immunofluorescence staining was used to detect the expression of Nrf2 in vivo. siRNA was used to evaluate the effect of Nrf2 in osteoclastogenesis. RESULTS: Sch suppresses RANKL-induced ROS production by regulating nuclear factor erythroid 2-related factor (Nrf2) in vitro and vivo. Mechanistically, Sch enhances the expression of Nrf2 by regulating the degradation of Nrf2. Further, Sch suppresses phosphorylation of P65 and its nuclear translocation, as well as the degradation of IκBα. Collectively, our findings reveal that Sch protects against OVX-induced bone loss by suppressing ROS via Nrf2. CONCLUSIONS: Our results showed the potential of anti-oxidant compound schisandrin A in the treatment of osteoporosis, highlighting Nrf2 as a novel promising target in osteoclast-related disease.

Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL-induced osteoclastogenesis.

Postmenopausal Osteoporosis (PMOP) is oestrogen withdrawal characterized of much production and activation by osteoclast in the elderly female. Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL-induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F-actin ring formation and tartrate-resistant acid phosphatase (TRAP) staining in dose-dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK-related trigger RANKL by phosphorylation JNK/ERK/p38-MAPK, IκBα/p65-NF-κB, and PI3K/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K-AKT-NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL-induced RANK-TRAF6 association and RANKL-related gene and protein markers such as NFATc1, Cathepsin K, MMP-9 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.

Finite element analysis of dual small plate fixation and single plate fixation for treatment of midshaft clavicle fractures.

BACKGROUND: Midshaft clavicle fractures are one of the most familiar fractures. And, dual small plate fixation has been reported as can minimize hardware-related complications. However, the biomechanical properties of the dual small plate fixation have not yet been thoroughly evaluated. Here, we report the results of a finite element analysis of the biomechanical properties of midshaft clavicle fractures treated with dual small plating and superior and anteroinferior single plate fixation. METHODS: A three-dimensional (3D) finite element model of the midshaft clavicle fractures was created, whose 4-mm transverse fracture gap, having an angle < 30 degree and devoid of overlapping triangles, was simulated between the fractured segments of the middle-shaft of the clavicle. The equivalent von Mises stress and displacement of the model was used as the output measures for analysis. RESULTS: No significant differences were found between dual plating, superior or anteroinferior single plating in cantilever bending, axial compression, and axial torsion. Dual plating with a smaller plate-screw construct is biomechanically eligible to compare with superior and anteroinferior single plate fixation using larger plate-screw constructs. CONCLUSIONS: This study demonstrated that larger plate-screw constructs for the treatment of simple are placed clavicular fractures; however, weight-bearing and exorbitant shoulder activity should be avoided after the operation. Therefore, dual plating may provide a viable option for fixing midshaft clavicle fractures and, thus, may be preferred for patients who need early activity.

Juglanin Inhibits Osteoclastogenesis in Ovariectomized Mice via the Suppression of NF-κB Signaling Pathways.

Bone metabolism is a physiological process that involves both osteoblasts and osteoclasts. Pathological changes of osteoclasts are commonly seen in osteoporosis diseases. Juglanin is a natural compound, reported to have an inhibitory effect on inflammation, oxidative stress and cancer progression. The purpose of this study is to explore the role that Juglanin plays on the osteoclast functions and underlying signaling pathways. In vitro study demonstrated that Juglanin had negative influence on osteoclastic differentiation by suppressing the transcription activity of osteoclastogenesis-related genes and proteins. To determine the underlying mechanism, Western blot was employed to show that Juglanin could significantly have negative effect on the phosphorylation of P50, P65, I-κB， ultimately suppressing the expression and transcriptional activity of nuclear factor of activated T cells (NFATc1). In vivo Juglanin treatment attenuate bone reducing in mice with removed ovary through suppressing osteoclast functioning. Taken together, our study demonstrated that in the molecular mechanism, JUG inhibited the expression of receptor activator of nuclear factor-κ B ligand (RANKL) induced NF - κ B signaling pathway, thus may play a vital part in preventing postmenopausal osteoporosis.

Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis.

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis-related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL-induced osteoclastogenesis by suppressing NF-kB, Ca2+, PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.

Juglanin ameliorates LPS-induced neuroinflammation in animal models of Parkinson's disease and cell culture via inactivating TLR4/NF-κB pathway.

Parkinson's disease (PD) is a common neuro-degenerative disorder, and novel therapeutic targets are required for the treatment of PD. Juglanin is a natural compound extracted from the crude Polygonum aviculare, exhibiting anti-inflammatory, anti-oxidant and anti-cancer activities. In our study, PD in mice was induced by systemic LPS treatment as evidenced by enhanced α-synuclein and reduced tyrosine hydroxylase (TH), which were reversed by juglanin treatment. Moreover, juglanin administration attenuated LPS-caused behavioral and memory impairments and reduced LPS-induced enhancement of neuro-degenerative markers, including amyloid ß (Aß) and p-Tau. Additionally, juglanin ameliorated synaptic functionality through promoting the expression of synaptic markers, such as SYP, PSD-95 and SNAP-25. Toll-like receptor 4 (TLR4) signaling in brain regulates neuroinflammation, contributing to neurodegenerative diseases. Furthermore, LPS induced neuroinflammation through the acceleration of various pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18) and Cyclooxygenase-2 (COX-2), via activating TLR4/nuclear factor (NF)-κB pathway in hippocampus of mice and microglia cells. Juglanin significantly reduced LPS-induced production of pro-inflammatory cytokines and blocked TLR4/NF-κB pathway. We also found that LPS-induced astrocytes (AST) activity was prevented by juglanin through down-regulating glial fibrillary acidic protein (GFAP) and Iba1 in vivo and in vitro. Together, our results indicated that juglanin ameliorated neuroinflammation-related memory impairment, and neurodegeneration through impeding TLR4/NF-κB, indicating its potential for PD prevention.